Diagnosis and treatment of hepatocellular carcinoma. Update consensus document from the AEEH, SEOM, SERAM, SERVEI and SETH / Diagnóstico y tratamiento del carcinoma hepatocelular. Actualización del documento de consenso de la AEEH, SEOM, SERAM, SERVEI y SETH

Hepatocellular carcinoma is the most common primary malignancy of the liver and one of the most frequent causes of death in patients with liver cirrhosis. Simultaneously with the recognition of the clinical relevance of this neoplasm, in recent years there have been important developments in the diagnosis, staging and treatment of HCC. Consequently, the Asociación Española para el Estudio del Hígado has driven the need to update clinical practice guidelines, continuing to invite all the societies involved in the diagnosis and treatment of this disease to participate in the drafting and approval of the document (Sociedad Española de Trasplante Hepático, Sociedad Española de Radiología Médica, Sociedad Española de Radiología Vascular e Intervencionista y Sociedad Española de Oncología Médica). The clinical practice guidelines published in 2009 accepted as Clinical Practice Guidelines of the National Health System has been taken as reference document, incorporating the most important advances that have been made in recent years. The scientific evidence for the treatment of HCC has been evaluated according to the recommendations of the National Cancer Institute (www.cancer.gov) and the strength of recommendation is based on the GRADE system.

El carcinoma hepatocelular es la neoplasia primaria de hígado más común y una de las causas de muerte más frecuentes en los pacientes afectos de cirrosis hepática. Simultáneamente al reconocimiento de la relevancia clínica de esta neoplasia, en los últimos años han aparecido novedades importantes en el diagnóstico, estadificación y tratamiento del carcinoma hepatocelular. Por tal motivo, desde la Asociación Española para el Estudio del Hígado se ha impulsado la necesidad de actualizar las guías de práctica clínica, invitando de nuevo a todas las sociedades involucradas en el diagnóstico y tratamiento de esta enfermedad a participar en la redacción y aprobación del documento (la Sociedad Española de Trasplante Hepático, la Sociedad Española de Radiología Médica, la Sociedad Española de Radiología Vascular e Intervencionista y la Sociedad Española de Oncología Médica). Se ha tomado como documento de referencia las guías de práctica clínica publicadas en 2009 aceptadas como Guía de Práctica Clínica del Sistema Nacional de Salud, incorporando los avances más importantes que se han obtenido en los últimos años. La evidencia científica en el tratamiento del carcinoma hepatocelular se ha evaluado de acuerdo con las recomendaciones del National Cancer Institute (www.cancer.gov) y la fuerza de la recomendación se basa en el sistema GRADE.

Tratamiento percutáneo e intraarterial del carcinoma hepatocelular / Percutaneous and intra-arterial treatment of hepatocellular carcinoma

La mayoría de pacientes con un carcinoma hepatocelular (CHC) no son candidatos a resección quirúrgica o trasplante hepático debido al estadio en el momento diagnóstico. Para este grupo de pacientes existen una serie de tratamientos locorregionales que consiguen una alta tasa de respuestas objetivas. La ablación percutánea está considerada la mejor opción terapéutica para el CHC (estadio 0/A-BCLC) no tributario de tratamiento quirúrgico. En el carcinoma hepatocelular multifocal sin invasión vascular ni extensión extrahepática (estadio B- BCLC) la única opción terapéutica que ha demostrado mejorar la supervivencia en estudios controlados y aleatorizados es la quimioembolización. La valoración de la efectividad de estos tratamientos se basa en la reducción del tumor viable y se realiza mediante TC, RM o US con contraste. En este trabajo se revisan las indicaciones, la técnica y la eficacia terapéutica de los distintos tratamientos locorregionales en el CHC (AU)

Most patients with hepatocellular carcinoma (CHC) are not candidates for surgical resection or liver transplantation because of their stage at the time of diagnosis. There are a series of locoregional treatments that achieve a high objective response rate in this group of patients. Percutaneous ablation is considered the best treatment option for CHC (BCLC stage 0/A) not amenable to surgical treatment. In multifocal hepatocellular carcinoma without vascular invasion or extrahepatic extension (BCLC stage B), the only treatment option that has been shown to improve survival in randomized controlled trials is chemoembolization. The evaluation of the effectiveness of these treatments is based on the reduction of viable tumor observed at CT, MRI, or contrast-enhanced US. In this article, we review the indications, technique, and therapeutic efficacy of the different locoregional treatments for CHC (AU)

[Percutaneous and intra-arterial treatment of hepatocellular carcinoma]. / Tratamiento percutáneo e intraarterial del carcinoma hepatocelular.

Most patients with hepatocellular carcinoma (CHC) are not candidates for surgical resection or liver transplantation because of their stage at the time of diagnosis. There are a series of locoregional treatments that achieve a high objective response rate in this group of patients. Percutaneous ablation is considered the best treatment option for CHC (BCLC stage 0/A) not amenable to surgical treatment. In multifocal hepatocellular carcinoma without vascular invasion or extrahepatic extension (BCLC stage B), the only treatment option that has been shown to improve survival in randomized controlled trials is chemoembolization. The evaluation of the effectiveness of these treatments is based on the reduction of viable tumor observed at CT, MRI, or contrast-enhanced US. In this article, we review the indications, technique, and therapeutic efficacy of the different locoregional treatments for CHC.

Successful treatment by selective arterial embolization of severe retroperitoneal hemorrhage secondary to bone marrow biopsy in post-polycythemic myelofibrosis.

Severe retroperitoneal hemorrhage represents an infrequent and serious complication of bone marrow biopsy. A 53-year-old man, diagnosed with polycythemia vera 12 years earlier, was submitted to a bone marrow biopsy due to the appearance of anemia with clinical and hematological features suggesting myelofibrotic transformation, a diagnosis that was confirmed by the marrow study. At 2 h of a right anterior iliac bone marrow trephine biopsy, the patient suddenly developed severe pain in the area of the biopsy, with antialgic flexion of the right leg. Computed tomographic (CT) scan of the abdomen showed a 5 x 9.5 cm hematoma in the right iliac and psoas muscles. The patient was initially managed with analgesics and transfusional support, but the pain persisted and a continuous fall in the hematocrit was observed in the following days. Angiographic examination of the right external iliac artery showed contrast extravasation arising from the circumflex iliac branch, which was embolized using polivinyl alcohol particles and one coil. Following such procedure, the patient recovered uneventfully and was discharged in good condition a few days later. This case illustrates the effectiveness of an endovascular approach in providing a fast and minimally invasive treatment for this life-threatening complication of bone marrow trephine biopsy.

Trombosis de la vena cava superior en un paciente en hemodiálisis / Superior vena cava thrombosis in a patient on hemodialysis

Presentamos el caso de un paciente con insuficiencia renal crónica terminal en programa de hemodiálisis crónica a través de un catéter Permcath® subclavio derecho, que presentó un síndrome de la vena cava superior (VCS) a consecuencia de una trombosis pericatéter que se trató inicialmente de manera conservadora mediante anticoagulación con mejoría inicial. Por reaparición de la clínica debió finalmente procederse a la retirada del Permcath®, angioplastia de la VCS y continuar la anticoagulación con dicumarínicos, con resolución clínica del cuadro y mejoría radiológica (AU)

We present a patient with end-stage renal disease on maintenace hemodialysis through a permanent catheter (Permcath®) on the right subclavian vein. One month after the catheter placement the patient exhibited a superior vena cava syndrome due to a pericatheter thrombosis. The patient was initially managed with anticoagulation with early clinical improvement. Nevertheless, the reappearance of the symptoms forced the removal of the catheter and percutaneous angioplasty of the superior vena cava. After those measures and anticoagulation with coumarin the patient remains stable with complete clinical resolution and angiographical improvement (AU)

Successful treatment of severe hemorrhagic cystitis after hemopoietic cell transplantation by selective embolization of the vesical arteries.

Hemorrhagic cystitis (HC) is a common and sometimes life-threatening complication of hemopoietic cell transplantation (HCT) occurring in 7-52% of transplant recipients. In this setting it is usually either related to the use of cyclophosphamide or to a viral infection (BK, JC viruses and adenovirus type 11). Treatment is based on hyperhydration, platelet and blood-cell transfusions, bladder irrigation and pain management. Where these measures have failed to control HC, numerous therapeutic approaches including surgery have been tried with poor success. We report two HCT patients with severe HC successfully treated with selective embolization of the vesical arteries.

Percutaneous repair of an iatrogenic laceration of the left bile duct with a covered stent.

The presence of biliary leaks after liver resections is not an unusual problem, especially after extended hepatectomies. The usual treatment of choice for biliary duct injuries is to decompress the biliary system with draining catheters. Persistent biliary fistulas are nevertheless a challenging problem when endoscopic or percutaneous approaches fail to achieve occlusion of the bile leakage. The authors report a bile duct injury after a right lobe hepatectomy treated percutaneously with placement of a covered stent. After 6 months, the patient was tube-free and without any episode of cholangitis or bile duct dilation. Longer follow-up will clarify the future role of this kind of device in biliary system lacerations.

Sonographic appearance of a retained surgical sponge in the neck.

We report the sonographic appearance and clinical course of a retained surgical sponge in the neck beginning 6 months after a partial thyroidectomy. Sonograms showed a subcutaneous curvilinear hyperechoic interface with marked acoustic shadowing obscuring the left side of the neck. Three months later, a fistulous tract could be seen. Surgical exploration revealed a florid foreign tissue reaction due to a retained surgical sponge. Early diagnosis of retained sponges is important to enable expeditious removal before complications develop.

Cortical laminar necrosis caused by immunosuppressive therapy and chemotherapy.

We report three patients in whom neurologic symptoms and cortical laminar necrosis developed after immunosuppressive treatment (cyclosporin A and FK 506) and polychemotherapy (vincristine and methotrexate). Initial neuroradiologic studies showed cortical and white matter involvement. Follow-up studies showed cortical hyper-intense lesions on T1-weighted MR images, consistent with cortical laminar necrosis. The clinical and radiologic data indicate that a transient hypoxic-ischemic process could have been responsible for the encephalic lesions in these three patients.

Inducible nitric oxide synthase in monocytes from patients with Graves' disease.

The presence of inducible nitric oxide synthase (iNOS) in fresh monocytes from patients with Graves' disease was demonstrated for the first time. Immunophenotypic analysis showed a profile reflecting a state of activation and differentiation of monocytes. Incubation of lymphomononuclear cells from healthy volunteers in the presence of synthetic peptides with sequences related to thyroid autoantigens (TSH receptor, thyroid peroxidase, or thyroglobulin) led to a stimulation of monocytes manifested by a change in phenotype and expression of iNOS. This expression did not take place on isolated monocytes, unless products associated with Th1 activity were present in the medium. Active peptides contained a characteristic "2-6-11" motif already described [López-Moratalla et al. (1995) Biochim. Biophys. Acta 1265, 181-188]. These results are suggestive of a new role for autoantigens in the pathogenesis of Graves' disease: that of inducing the expression of iNOS and activating the monocyte possibly underlying the autoimmune response.

p53 gene mutations and protein nuclear accumulation are early events in intestinal type gastric cancer but late events in diffuse type.

We screened for p53 alterations in 71 early gastric cancers of differing histological types and growth patterns, 18 advanced cancers of diffuse type, 19 dysplastic lesions, and 12 extensive intestinal metaplasia cases. Tumors were investigated for gene mutations (exons 5-8) with PCR-based denaturing gradient gel electrophoresis and sequencing techniques, and for protein accumulation with immunohistochemical methods. Nontumor samples were studied with immunohistochemistry alone. Of the early cancers, intestinal tumors showed a much higher p53 mutation frequency (41%) than did diffuse cancers (4%). When comparing early and advanced tumors of the same type, we observed a similarity in mutation frequency (41 versus about 50%) for intestinal tumors, and a significant increase for diffuse tumors (from 4 to 33%). Immunopositive case distribution between tumor types and stages paralleled that of mutated cases. Immunohistochemical and genetic analysis gave concordant results for all samples with gene mutations. Eighteen of the 65 (28%) nonmutated tumors displayed significant immunoreactivity. Early tumors that massively penetrated the submucosa, i.e., the early tumors for which prognosis is worst, showed the highest frequency both of p53 gene mutation and of nonmutated protein accumulation. Twelve of 19 dysplastic lesions showed significant immunoreactivity, whereas intestinal metaplasias proved unreactive in all but a few cells. Our results yield two implications: that p53 alterations have a crucial and early role in gastric carcinogenesis of intestinal type, likely acting at the transition step between metaplasia and dysplasia; and that the alterations are mainly associated with tumor progression in cancer of diffuse type.

Erosive arthritis in relapsing polychondritis.

We report the case history of a 57 year old man who has suffered from typical deforming, relapsing polychondritis for 13 years. He has also developed erosive destructive seronegative polyarthritis involving some of his distal interphalangeal, proximal interphalangeal, metacarpophalangeal, intercarpal, wrist, intertarsal and metatarsophalangeal joints. The distribution of joint involvement in the small joints of the hands and feet is asymmetrical. Both hips and knee joints have also been involved necessitating bilateral total hip and right total knee replacement. The articular associations with relapsing polychondritis are discussed.